Phase I/II Study of Bi-weekly Irinotecan plus Cisplatin in the Treatment of Advanced Gastric Cancer

Abstract

Objectives: To conduct a phase I/II study of irinotecan with cisplatin to establish a recommended dose, and assess the safety, efficacy and feasibility of this regimen in unresectable advanced or recurrent gastric cancer. Patients and Methods: In the phase I portion of the study, patients received a fixed dose of cisplatin (30 mg/m²) with escalating doses of irinotecan, ranging from 30 mg/m² to 70 mg/m², on days 1 and 15. In the phase II portion of the study, 40 patients were evaluated for response and safety at the recommended dose. Results: Eighteen patients were enrolled in the phase I study. Dose-limiting toxicity (diarrhea and neutropenia) appeared at the irinotecan dose of 70 mg/m². Therefore, the recommended irinotecan dose was 60 mg/m². In the phase II study, 40 patients received cisplatin (30 mg/m²) plus irinotecan (60 mg/m²). Twenty-five out of 40 patients had received prior chemotherapy. The median number of cycles was 3.5. The response rate was 32.5% (13/40) overall, and 53.3% (8/15) in patients without prior chemotherapy. The median time to tumor progression (TTP) was 162 days. The median survival time was 288 days. Four patients (10%) developed grade 4 neutropenia and 3 patients (7.5%) developed grade 4 anemia. The only observed non-hematological toxicity at grade 3 or higher was diarrhea, seen in 2.5% (1/40) of the patients. Conclusion: Bi-weekly administration of irinotecan and cisplatin is safe and active for the management of unresectable advanced or recurrent gastric cancer.